Novel flavonoid has therapeutic potential for postmenopausal osteoporosis
MedWire News: A novel flavonoid isolated from the bark of the Himalayan Elm tree improves bone mineral density (BMD) and trabecular microarchitecture in rats with ovariectomy-induced bone loss, Indian researchers report.
The compound, 6-C-β-D-glucopyranosyl-(2S,3S)-(+)-3’,4’,5,7-tetrahydroxyflavanone (GTDF)/Ulmoside A, was isolated from the extract of Ulmus wallichiana, which is traditionally used for rapid fracture healing in parts of India.
Naibedya Chattopadhyay (Central Drug Research Institute, Lucknow) and colleagues investigated GDTF’s ability to prevent ovariectomy-induced bone loss in rats. They found that ovariectomized rats treated with oral GTDF at 1.0 or 5.0 mg/kg daily for 12 weeks had significantly higher BMD in the trabecular (distal femur, proximal tibia, and vertebrae) and cortical (femur shaft) regions, compared with ovariectomized rats that received the vehicle only.
Furthermore, BMD levels in the GTDF-treated rats were comparable with those of sham-operated rats treated with the vehicle only.
Micro-computed tomography demonstrated that ovariectomized rats treated with GTDF at 5.0 mg/kg/day, but not 1.0 mg/kg/day, had significantly better bone microarchitectural parameters than the ovariectomized rats that received the vehicle only.
Serum osteocalcin and urinary C-terminal teleopeptide of Type I collagen levels in ovariectomized rats treated with GTDF at both doses were significantly lower than in ovariectomized rats that received the vehicle only. However, levels were comparable to ovariectomized rats that received 17β-estradiol and sham-operated rats that received the vehicle.
“These data suggest that GTDF inhibits bone turnover rate that is characteristically increased under estrogen deficiency,” remark Chattopadhyay et al.
Of note, neither dose of GTDF was associated with uterine estrogenicity.
Pharmacokinetic analysis revealed that GTDF achieved a maximum plasma concentration of 40.67 ng/ml at approximately 1 hour, indicating slow absorption. Its absolute bioavailability was found to be 1.04% with a plasma elimination half-life of approximately 5 hours.
“Our study demonstrates that daily oral administration of GTDF at a favorable dose of 5.0 mg/kg/day mitigates ovariectomy-induced deterioration of bone strength and maintains trabecular microarchitecture without a uterine hyperplastic effect, thus raising the possibility of an alternative strategy for the development of new treatment for postmenopausal osteoporosis,” Chattopadhyay and co-authors conclude in the journal Menopause.
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By Laura Dean